Beta-N-acetylhexosaminidases of glycosyl hydrolase family 20 (GH20) catalyze the removal of beta-1,4-linked N-acetyl-D-hexosamine residues from the non-reducing ends of N-acetyl-beta-D-hexosaminides including N-acetylglucosides and N-acetylgalactosides. These enzymes are broadly distributed in microorganisms, plants and animals, and play roles in various key physiological and pathological processes. These processes include cell structural integrity, energy storage, cellular signaling, fertilization, pathogen defense, viral penetration, the development of carcinomas, inflammatory events and lysosomal storage disorders. The GH20 enzymes include the eukaryotic beta-N-acetylhexosaminidases A and B, the bacterial chitobiases, dispersin B, and lacto-N-biosidase. The GH20 hexosaminidases are thought to act via a catalytic mechanism in which the catalytic nucleophile is not provided by the solvent or the enzyme, but by the substrate itself.
Structure:1NP0_A; Homo sapiens Lysosomal Beta-Hexosaminidase isoform B (HexB) beta subunit, binds an intermediate analog NAG-Thiazoline (N-acetyl-beta-D-glucosamine-thiazoline).
Structure:1M01_A; Streptomyces plicatus Beta-hexosaminidase bound with product (GlcNAc), contacts at 3.5A. N-acetyl-D-glucosamine
Comment:For 1M01_A, the most C-terminal active site Asp residue plays a critical role in substrate-assisted catalysis by orienting the 2-acetamido group and stabilizing the transition state.
Structure:2GK1_A/B; Homo sapiens Lysosomal Beta-Hexosaminidase isoform A (HexA), alpha and beta subunits each bind an intermediate analog NAG-Thiazoline (N-acetyl-beta-D-glucosamine-thiazoline), contacts at 4 A.
Comment:there are two active sites in the HexA heterodimer, one in the alpha subunit, one in the beta subunit. A Tyr residue from the beta subunit is found in the active site of the alpha subunit and vice versa.
Jiyao W et al.(2023). "The conserved domain database in 2023.",